{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T01:43:21Z","timestamp":1782783801937,"version":"3.54.5"},"reference-count":96,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","award":["3661"],"award-info":[{"award-number":["3661"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Multiple System Atrophy UK Trust","award":["2024\/MSAT_MX01"],"award-info":[{"award-number":["2024\/MSAT_MX01"]}]},{"DOI":"10.13039\/100018889","name":"Multiple System Atrophy Coalition","doi-asserted-by":"crossref","award":["2020-05-001"],"award-info":[{"award-number":["2020-05-001"]}],"id":[{"id":"10.13039\/100018889","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation","doi-asserted-by":"publisher","award":["MJFF-024029"],"award-info":[{"award-number":["MJFF-024029"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brain Precision Greece 2.0 program","award":["TAEDR-0535850"],"award-info":[{"award-number":["TAEDR-0535850"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple lines of evidence extracted from human post-mortem brain material and cellular and animal models of concomitant proteinopathies cumulatively suggest that the neuronal protein \u03b1-Synuclein exerts a strong influence on the pathogenesis of neurodegenerative comorbidities, collectively termed \u03b1-Synucleinopathies. Accumulation of \u03b1-Synuclein-positive inclusions in neurons or oligodendrocytes is the main histopathological hallmark of Parkinson\u2019s disease (PD) or multiple system atrophy (MSA), respectively. In addition, various pieces of data indicate that components of the autophagy-lysosomal pathway are altered in the context of \u03b1-Synucleinopathies. \u03b1-Synuclein itself is degraded by autophagy; however, aberrant protein conformations may impair lysosomal function. Genetic PD often involves components of the lysosome, including common genetic mutations in GBA1, which encodes for the lysosomal enzyme \u03b2-glucocerebrosidase. Alterations in lysosomal components that correlate with a commensurate increase in \u03b1-Synuclein deposition have been widely observed in PD brains. However, corresponding data in the context of MSA are emerging but remain less extensive than PD. In the current review, we focus on the pathological features as well as the impairments in the autophagy\u2013lysosome pathway (ALP) that are associated with MSA and discuss the current challenges and future directions of therapeutic strategies targeting autophagy in experimental MSA-like models.<\/jats:p>","DOI":"10.3390\/ijms262010204","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:20:12Z","timestamp":1760973612000},"page":"10204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Autophagy\u2013Lysosome Pathway in Multiple System Atrophy Pathogenesis: The Best Is Yet to Come"],"prefix":"10.3390","volume":"26","author":[{"given":"Panagiota","family":"Mavroeidi","sequence":"first","affiliation":[{"name":"Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7038-0780","authenticated-orcid":false,"given":"Maria","family":"Xilouri","sequence":"additional","affiliation":[{"name":"Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","first-page":"e10741","article-title":"Multiple System Atrophy\u2014Cerebellar Type: Clinical Picture and Treatment of an Often-Overlooked Disorder","volume":"12","author":"Ortiz","year":"2020","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0022-510X(89)90219-0","article-title":"Glial Cytoplasmic Inclusions in the CNS of Patients with Multiple System Atrophy (Striatonigral Degeneration, Olivopontocerebellar Atrophy and Shy-Drager Syndrome)","volume":"94","author":"Papp","year":"1989","journal-title":"J. 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